Weber, Georg F.;
Gaertner, Florian C.;
Erl, Wolfgang;
Janssen, Klaus-Peter;
Blechert, Birgit;
Holzmann, Bernhard;
Weighardt, Heike;
Essler, Markus
IL-22-Mediated Tumor Growth Reduction Correlates with Inhibition of ERK1/2 and AKT Phosphorylation and Induction of Cell Cycle Arrest in the G2-M Phase
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Medientyp:
E-Artikel
Titel:
IL-22-Mediated Tumor Growth Reduction Correlates with Inhibition of ERK1/2 and AKT Phosphorylation and Induction of Cell Cycle Arrest in the G2-M Phase
Beteiligte:
Weber, Georg F.;
Gaertner, Florian C.;
Erl, Wolfgang;
Janssen, Klaus-Peter;
Blechert, Birgit;
Holzmann, Bernhard;
Weighardt, Heike;
Essler, Markus
Erschienen:
The American Association of Immunologists, 2006
Beschreibung:
<jats:title>Abstract</jats:title>
<jats:p>IL-22 is a recently discovered cytokine of the IL-10 family that binds to a class II cytokine receptor composed of IL-22R1 and IL-10R2c and influences a variety of immune reactions. As IL-22 has also been shown to modulate cell cycle and proliferation mediators such as ERK1/2 and JNK, we studied the role of IL-22 in proliferation, apoptosis, and cell cycle regulation in EMT6 murine breast cancer cells in vitro and in vivo. In this study, we report that murine breast cancer cells express functional IL-22R as indicated by RT-PCR studies, immunoblotting, and STAT3 activation assays. Importantly, IL-22 exposure of EMT6 cells resulted in decreased levels of phosphorylated ERK1/2 and AKT protein kinases, indicating an inhibitory effect of IL-22 on signaling pathways promoting cell proliferation. Furthermore, IL-22 induced a cell cycle arrest of EMT6 cells in the G2-M phase. IL-22 reduced EMT6 cell numbers and the proliferation rate by ∼50% as measured by [3H]thymidine incorporation. IL-22 treatment of EMT6 tumor-bearing mice lead to a decreased tumor size and a reduced tumor cell proliferation in vivo, as determined by 3′-deoxy-3′-fluorothymidine-positron emission tomography scans. Interestingly, IL-22 did not induce apoptosis, as determined in annexin V binding assay and caspase-3 activation assay and had no effect on angiogenesis in vivo. In conclusion, our results indicate that IL-22 reduced tumor growth by inhibiting signaling pathways such as ERK1/2 and AKT phosphorylation that promote tumor cell proliferation in EMT6 cells. Therefore, IL-22 may play a role in the control of tumor growth and tumor progression.</jats:p>